This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The project is focusing on the complex between SHEP1 and p130Cas. These two proteins represent prototypes of a set of proteins consisting of SHEP1, SHEP2, SHEP3 and p130Cas and pCasL which have been found to be important factors in a spectrum of diseases in particular breast cancer.Our crystals comprise the complex of the GEF domain of SHEP1 and the SHEP interaction domain of p130Cas. The structure will give for the first time important insight into (i) the GEF domain of SHEP proteins and how they compare to other GEFs in order to predict its action on members of the Ras protein family, (ii) the structure of the SHEP interaction domain of p130Cas and (iii) how binding of Cas proteins affect the GEF function of SHEP proteins. No high resolution data is currently available to answer these questions. Obtaining high quality data using synchrotron radiation will be a crucial factor in deciphering the structure. The structure of the SHEP1/p130Cas complex will provide invaluable insight into mechanistic questions of these central regulatory proteins and has also the potential to help in the design of therapeutics in cancer treatment.